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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2014  |  Volume : 25  |  Issue : 2  |  Page : 362-366
Effect of kidney transplantation on early and late post-transplant prostate-specific antigen levels

1 Department of Urology, Mashhad University of Medical Sciences, Mashhad, Iran
2 Department of Nephrology, Mashhad University of Medical Sciences, Mashhad, Iran

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Date of Web Publication11-Mar-2014


The aim of this study was to determine the effect of kidney transplantation on serum prostate-specific antigen (PSA) levels. Forty patients who were on peritoneal dialysis or hemodialysis underwent kidney transplantation at our department. The immunosuppressive protocol was uniform during the study period. The creatinine and prostate specific antigen (PSA) levels, both free and total, were measured by immunofluorometric assays immediately before transplantation and on post-transplant Days 1, 7, 90 and 180. The mean age of the patients was 49.97 ± 4.4 years. After transplantation, there was a significant decrease in free PSA, but there was no correlation between total PSA and serum creatinine. Free PSA levels were significantly decreased after kidney transplantation but total PSA remained unchanged. This was observed in post-transplant patients irrespective of whether they had delayed graft function, slow graft function or immediate graft function during the observed period. Therefore, total PSA can be used as a marker for prostate cancer screening after kidney transplantation.

How to cite this article:
Mahdavi R, Zeraati A, Tavakkoli M, Aghamohammadpour K, Ghoreifi A. Effect of kidney transplantation on early and late post-transplant prostate-specific antigen levels. Saudi J Kidney Dis Transpl 2014;25:362-6

How to cite this URL:
Mahdavi R, Zeraati A, Tavakkoli M, Aghamohammadpour K, Ghoreifi A. Effect of kidney transplantation on early and late post-transplant prostate-specific antigen levels. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2020 Jul 12];25:362-6. Available from: http://www.sjkdt.org/text.asp?2014/25/2/362/128545

   Introduction Top

The expansion of organ transplant criteria, including older donors and recipients, combined with improved allograft survival has enhanced the relevance of prostate cancer screening in this group. [1] Despite the progress in the understanding, diagnosis and treatment of prostate cancer, manv asoects of the disease still remain controversial. This is particularly true in the transplant population. [1] Prostate-specific antigen (PSA) levels are very important in the detection and monitoring of patients with prostate cancer. PSA is a 33 kilodalton (kDa) glycoprotein produced by prostatic epithelial cells. It has two main molecular forms in blood; free PSA (f-PSA) and complexed with α-1-antichymotrypsin or α-2-macroglubulin (c-PSA). c-PSA is the predominant fraction and more stable and weighs about 90 kDa. The sum of c-PSA and f-PSA makes total PSA (t-PSA). [2],[3],[4] The free PSA percentage (f-PSA%) is an aid in distinguishing prostate cancer from benign prostatic conditions. The free percentage is calculated using the total and free PSA results. Combination of low molecular weight and short half-life (4-33 h) for f-PSA suggests elimination by glomerular filtration. In contrast, c-PSA has a longer half-life and about three-fold larger molecular weight; therefore, other routes of elimination such as liver metabolism is suggested. [5],[6],[7],[8] Renal function can therefore be expected to affect the relative proportions of the two PSA forms in men with renal failure. This has been confirmed by the findings among male patients on hemodialysis [9],[10],[11],[12] as well as those on peritoneal dialysis treatment. [12] Therefore, use of the current clinical limits for %f-PSA could cause some men with prostate cancer to be misdiagnosed as having benign disease. We conducted this study to determine the results of kidney transplantation on PSA levels as an important screening tool for prostate cancer.

   Materials and Methods Top

This cohort study consisted of 40 men all over 45 years old with end-stage renal disease (ESRD) who were kidney transplantation candidates at our Department of Urology and Transplantation, Imam Reza Hospital, Mashhad University of Medical Sciences.

The creatinine and PSA levels (free and total) were measured by immunofluromteric assays immediately before kidney transplantation and on post-transplant Days 1, 7, 90 and 180. The immunosuppressive protocol was the same in all patients, with azathioprine (imuran), mycophenolate mofetil (MMF) and prednisolone and anti-thymocyte globulin (ATG) given for those with delayed graft function (DGF). There were three groups according to renal function and creatinine levels in the first post-transplant week.

The first group included patients with immediate graft function (IGF) with Cr <2.5 mg/dL in the first week. The second group included patients with slower graft function (SGF) with a Cr >2.5 mg/dL on the first week without needing dialysis and the third group included patients with DGF who needed hemodialysis in the first week after transplantation. We analyzed the results with SPSS-15 software using paired t-test with Pearson correlation and P-value <0.05 was considered significant.

   Results Top

The mean age was 49.97 ± 4.41 years. The baseline t-PSA was 2.50 ± 0.57 and it was 2.44 ± 0.59, 2.43 ± 0.59, 2.40 ± 0.69 and 2.35 ± 0.69 on the 1 st , 7 th , 90 th and 180 th post-transplant days, respectively. The baseline f-PSA and its changes on the same days were 1.08 ± 0.44, 0.64 ± 0.31, 0.64 ± 0.32, 0.66 ± 0.36 and 0.65 ± 0.41, respectively. There were no significant changes in the pre- and post-transplant t-PSA, but f-PSA showed a significant decrease in the post-transplant patients (P-value <0.05).

Of the 40 kidney transplant recipients, DGF was observed in five (12.5%) patients. Pre-transplant t-PSA was 2.58 ± 0.68, and it showed no significant change on the post-transplant evaluations [Table 1]. SGF was observed in six (15%) patients and pre-transplant and post-transplant. No significant statistical change in t-PSA and f-PSA was observed in this group. Changes of t-PSA and f-PSA are shown in [Table 2].
Table 1: PSA levels in DGF patients.

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Table 2: PSA levels in SGF patients.

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Finally, the IGF group included 29 (72.5%) patients. Pre-transplant and post-transplant changes in t-PSA and f-PSA are shown in [Table 3]. In this group, t-PSA did not show any significant changes before and after transplantation, but f-PSA levels showed a significant decrease after transplantation.
Table 3: PSA levels in IGF patients.

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   Discussion Top

Renal transplant recipients (RTRs) have a four- to 20-fold higher risk for de novo cancers compared with the general population, especially skin cancer and post-transplant lymphoproliferative disorders (PTLD). [13],[14],[15] Genitourinary (GU) malignancies have been reported to be the second most common malignancies in the RTR population in the United States. [16] Earlier studies of prostate cancer incidence in RTR found it to be similar to the general population, but with the increased RTR lifespan and recipient age at the time of transplantation and better screening practices, prostate cancer has become frequent in this population, two- to five-fold higher than that in the general population. [17],[18] Also, in a study, Dicapua et al stated that 29 de novo tumors were diagnosed in the 1751 transplanted patients, while 11 patients (38%) were diagnosed with prostate cancer. [19] Therefore, prostate cancer was the most common urologic cancer seen in these patients. These data were also confirmed in other studies. [19]

First purified in 1979, PSA is a single-chain, 33 kDa glycoprotein produced only by prostatic epithelial cells, which has structural homology with serine proteases. t-PSA and f-PSA are frequently measured to differentiate between benign and malignant disease of prostate, and a higher percent of f-PSA indicates a lesser risk of malignancy. [4] Several studies were performed to determine the affect of renal failure and dialysis on serum PSA, which led to different results. Several reports confirm that men with terminal renal failure requiring chronic dialysis have significantly higher f-PSA% compared with men without known renal dysfunction. [9],[10],[11],[12] Douville and Tiberi found a significantly higher serum f-PSA and f-PSA% in dialysis patients compared with controls. Djavan et al found that f-PSA and f-PSA% were significantly higher among patients on hemodialysis. [11]

But, limited data are available with respect to PSA screening in the transplanted patients as well as prostate cancer behavior and treatment outcomes. [11] Most data regarding PSA screening and outcomes of prostate cancer treatment in the transplant population are limited to case reports and small series, and primarily involve renal insufficiency. [20] Kamali and Zargar in their study stated that there was a significant decrease (30% of original levels) in serum f-PSA at post-transplant Day 6 in all patients, and there was no significant changes of total PSA at the same time. [21] These data were in agreement with the result of the Brunn et al study. [22] They measured f-PSA and c-PSA in patients with renal failure before and after successful renal transplantation, and found that the median pre-transplant levels of f-PSA were significantly higher compared with controls.

Median f-PSA also declined rapidly in the first 6 h after transplantation, while the median c-PSA increased, consistent with renal filtration of f-PSA, which has a smaller molecular size than c-PSA. [22] Fischer et al measured the f-PSA% in patients with renal failure and after renal transplantation. f-PSA% was significantly higher among patients with renal failure compared with renal transplant patients and with controls. Among patients with prostate cancer and benign prostate disease, f-PSA% was significantly higher among patients with renal failure compared with non-uremic controls. [23] Chamie et al in their study concluded that only immunosuppression with sirolimus independently impacted post-transplant PSA. Their data strongly suggest that sirolimus is associated with a significant PSA decrease in kidney recipients. [24] In our study, the immunosuppressive protocol was the same in all patients, with imuran, MMF and prednisolone, and did not contain any drug that interferes with PSA clearance. Also, there are some situations that may change PSA values like inflammations and traumatic interventions. There was no significant inflammation in any patient and only catheterization with a Foley catheter was performed in an identical manner in all patients.

In our study, f-PSA was reduced significantly after renal transplant, which was in agreement with the studies stated above. Also, we found that t-PSA did not change significantly after transplant, and this also was in agreement with the previous studies that stated this high molecular weight substance was only minimally influenced by glomerular filtration and renal failure.

There is no study about the relationship between f-PSA and t-PSA and different groups of transplanted patients according to their renal function (IGF, SGF and DGF). In our study, there was no significant change in t-PSA after transplant in all patients. This can be explained by the fact that this high molecular weight substance cannot be filtered by the renal glomerules, and our results are in agreement with

previous studies that also stated this fact. [9],[10],[11],[12],[20],[21],[22] But, there was a significant decrease in the f-PSA level after transplant, which had a direct relationship with the serum creatinine of the patients. This relationship was also seen in the patients with IGF. Therefore, it seems likely that f-PSA levels correlate with glomerular filtration rate, and, the better the renal function, the lower the serum creatinine and lower the f-PSA level. Although we had expected that f-PSA will decrease only later than the IGF group, the other two groups (SGF and DGF) did not show any significant changes postoperatively. It seems likely that longer follow-up is needed to show the probable further PSA changes in these patients.

Because of the changes in f-PSA and f-PSA% to total PSA levels, it seems that new cut-off levels for screening of prostate cancers in ESRD patients are required. Total PSA seems to be a more useful factor in screening of prostate cancer in patients with ESRD because its level dose not change significantly after renal transplantation.

Conflict of interest: None

   References Top

1.Breyer BN, Whitson JM, Freise CE, Meng MV. Prostate cancer screening and treatment in the transplant population: Current status and recommendations. J Urol 2009;181:2018-26.  Back to cited text no. 1
2.Stenman UH, Leinonen J, Alfthan H, Rannikko S, Tuhkanen K, Alfthan O. A complex between prostate-specific antigen and alpha 1-anti-chymotrypsin is the major form of prostate-specific antigen in serum of patients with prostatic cancer: Assay of the complex improves clinical sensitivity for cancer. Cancer Res 1991; 51:222-6.  Back to cited text no. 2
3.Lilja H, Christensson A, Dahlen U, et al. Prostate-specific antigen in serum occurs predominantly in complex with alpha 1 -antichymotrypsin. Clin Chem 1991;37:1618-25.  Back to cited text no. 3
4.Christensson A, Bjbrk T, Nilsson O, et al. Serum prostate specific antigen complexed to alpha 1-antichymotrypsin as an indicator of prostate cancer. J Urol 1993;150:100-5.  Back to cited text no. 4
5.Partin AW, Piantadosi S, Subong EN, et al. Clearance rate of serum-free and total PSA following radical retropubic prostatectomy. Prostate Suppl 1996;7:35-9.  Back to cited text no. 5
6.Lilja H, Haese A, Bjbrk T, et al. Significance and metabolism of complexed and noncomplexed prostate specific antigen forms, and human glandular kallikrein 2 in clinically localized prostate cancer before and after radical prostatectomy. J Urol 1999;162:2029-35.  Back to cited text no. 6
7.Kilic S, Yalcinkaya S, Guntekin E, Kukul E, Deger N, Sevuk M. Determination of the site of metabolism of total, free, and complexed prostate-specific antigen. Urology 1998;52:470-3.  Back to cited text no. 7
8.Birkenmeier G, Struck F, Gebhardt R. Clearance mechanism of prostate specific antigen and its complexes with alpha2-macroglobulin and alphal-antichymotrypsin. J Urol 1999; 162: 897-901.  Back to cited text no. 8
9.Sasagawa I, Kubota Y, Hayami S, et al. Serum levels of total and free prostate specific antigen in men on hemodialysis. J Urol 1998;160:83-5.  Back to cited text no. 9
10.Douville P, Tiberi M. Effect of terminal renal failure on the ratio of free to total prostate-specific antigen. Tumour Biol 1998;19:113-7.  Back to cited text no. 10
11.Djavan B, Shariat S, Ghawidel K, et al. Impact of chronic dialysis on serum PSA, free PSA, and free/total PSA ratio: Is prostate cancer detection compromised in patients receiving long-term dialysis? Urology 1999;53:1169-74.  Back to cited text no. 11
12.Bruun L, Bjbrk T, Lilja H, Becker C, Gustafsson O, Christensson A. Percent-free prostate specific antigen is elevated in men on haemodialysis or peritoneal dialysis treatment. Nephrol Dial Transplant 2003;18:598-603.  Back to cited text no. 12
13.Danpanich E, Kasiske BL. Risk factors for cancer in renal transplant recipients. Transplantation 1999;68:1859-64.  Back to cited text no. 13
14.Kasiske BL, Snyder JJ, Gilbertson DT, Wang C. Cancer after kidney transplantation in the United States. Am J Transplant 2004;4:905-13.  Back to cited text no. 14
15.Kessler M, Jay N, Molle R, Guillemin F. Excess risk of cancer in renal transplant patients. Transpl Int 2006;19:908-14.  Back to cited text no. 15
16.US Renal Data System (USRDS). Annual Report: Atlas of End Stage Renal Disease in the United States. In Health NIo ed. National Institutes of Diabetes and Digestive and Kidney Disease, Besthesda, MD, 2007.  Back to cited text no. 16
17.Penn I. Occurrence of cancers in immunosuppressed organ transplant recipients. Clin Transpl 1998:147-58.  Back to cited text no. 17
18.Kleinclauss F, Gigante M, Neuzillet Y, et al. Prostate cancer in renal transplant recipients. Nephrol Dial Transplant 2008;23:2374-80.  Back to cited text no. 18
19.di Capua Sacoto C, Lujan Marco S, Bahilo Mateu P, Budia Alba A, Pontones Moreno JL, Jimenez Cruz JF. [De novo urological neoplasms in kidney transplant patients: Experience in 1,751 patients]. Actas Urol Esp 2010;34:88-94.  Back to cited text no. 19
20.Joseph DA, Thompson T, Saraiya M, Werny DM. Association between glomerular filtration rate, free, total, and percent free prostate-specific antigen. Urology 2010;76:1042-6.  Back to cited text no. 20
21.Kamali K, Zargar MA. Effects of renal transplantation on serum-free and total PSA levels. Transplant Proc 2007;39:1027-8.  Back to cited text no. 21
22.Bruun L, Ekberg H, Bj0rk T, Lilja H, H0glund P, Christensson A. Rapid elimination by glomerular filtration of free prostate specific antigen and human kallikrein 2 after renal transplanttation. J Urol 2004;171:1432-5.  Back to cited text no. 22
23.Fischer K, Hamza A, Wicht A, Loertzer H, Fornara P. Shift of the f/t-PSA quotient in relation to renal insufficiency: Consequences for the early detection of prostate carcinoma in patients with terminal renal failure. Anticancer Res 2007;27:1945-8.  Back to cited text no. 23
24.Chamie K, Ghosh PM, Koppie TM, Romero V, Troppmann C, deVere White RW. The effect of sirolimus on prostate-specific antigen (PSA) levels in male renal transplant recipients without prostate cancer. Am J Transplant 2008;8:2668-73.  Back to cited text no. 24

Correspondence Address:
Alireza Ghoreifi
Department of Urology, Mashhad University of Medical Sciences, Mashhad
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DOI: 10.4103/1319-2442.128545

PMID: 24626004

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  [Table 1], [Table 2], [Table 3]


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